In one aspect the present invention relates to plasmapheresis, that is, the separation of blood into a plasma fraction and a cellular component fraction, In another aspect, the present invention relates to plasmapheresis effected by ultrafiltration on a continuous basis, that is, a process whereby blood is withdrawn from a donor, separated into cellular component and plasma fractions, and the cellular components returned, in admixture with an appropriate amount of replacement fluid, to the donor at approximately the rate at which blood is being withdrawn. In still a further aspect, the present invention relates to an apparatus for the continuous separation of blood into plasma and cellular component fractions by ultrafiltration.
To appreciate the nature of the present invention, as well as the difficulties and complications which attend the separation of blood into cellular component and plasma fractions, a brief discussion of the makeup of blood is useful. Approximately 45% of the volume of blood is in the form of cellular components. These cellular components include red cells, also referred to as erythrocytes, white cells, also referred to as leukocytes, and platelets. Plasma makes up the remaining 55% of the volume of blood. Basically, plasma is the fluid portion of the blood which suspends the cells and comprises a solution of approximately 90% water, 7% protein and 3% of various other organic and inorganic solutes. As used herein, the term "plasmapheresis" refers to the separation of a portion of the plasma fraction of the blood from the cellular components thereof. Thus, plasmapheresis effected by ultrafiltration is to be distinguished from ultrafiltration of blood into a fraction containing cellular materials and the protein constituents of the plasma and a fraction comprising the aqueous portion of the plasma.
Separation of blood into a plasma fraction and a cellular component fraction is desirable for many medical reasons. For example, separation of blood into plasma fractions and cellular component fractions provides for a collection of plasma alone, with the cellular components being returned to the donor with a suitable portion of replacement fluid. Thus, continuous plasmapheresis provides for the collection of plasma from donors without the removal of the cellular components of the blood. Secondly, continuous plasmapheresis can be used therapeutically to remove pathogenic substances contained in the plasma portion of the blood. This can be accomplished by separating the cellular components from the diseased plasma and returning the cellular components to the patient in admixture with a suitable replacement fluid, or by further fractionating the patient's plasma to remove the unwanted substances and returning a major portion of the patient's plasma with the cellular components. Finally, a continuous plasmapheresis process can be employed for diagnostic purposes wherein plasma is separated on a continuous basis from the cellular components and analyzed to detect disease-causing substances or conditions therein.
In the past, ultrafiltration has been used on a continuous basis as a substitute for, or in combination with, dialysis methods in artificial kidneys and the like and has also been employed in batch-type plasmapheresis processes. For example, U.S. Pat. No. 3,579,441 to Brown, issued May 18, 1971, discloses a means for purifying the blood by continuously ultrafiltering the blood to separate macromolecular substances having molecular weights higher than 10,000, or so, and generally at least 40,000-50,000 which includes blood cells, fat droplets, lipids, high molecular weight polypeptides and the like from the remaining ultrafiltered aqueous portion of the blood. Such operations are not true plasmapheresis processes, as defined herein, because blood is separated not into plasma and cellular component fractions but rather into macromolecular fractions (containing cellular components and portions of the plasma) and a low molecular weight fraction which contains the waste products which must be removed in an artificial kidney-type process. Further, ultrafiltration has been used for plasmapheresis on a noncontinuous basis. For example, U.S. Pat. No. 3,705,100 to Blatt et al., issued Dec. 5, 1972, discloses a process and apparatus for a blood fractionating process. However, the process and apparatus disclosed therein is for the fractionating of blood on a batch basis, that is, on a noncontinuous basis whereby blood is held in a reservoir and then circulated in a spiral flow over an ultrafiltration membrane to effect separation.
In any plasmapheresis-type process effected by ultrafiltration there are various problems which occur during the fractionating of the blood by passing it in a parallel flow pattern over a membrane, with a transmembrane pressure sufficient to push the plasma portion of the blood therethrough, while allowing the cellular component portion of the blood to remain thereon. One of these problems is that the flow rates must be controlled fairly closely. Thus, if the flow rate employed is too fast, turbulence will occur within the ultrafiltration cell which may cause hemolysis and the general destruction of cellular components. On the other hand, if flow rates and transmembrane pressures are not controlled adequately the cellular and macromolecular components of the blood will tend to clog up the membrane thus significantly slowing the ultrafiltration rate. Such clogging can also cause hemolysis to occur. While the above stated problems attend any ultrafiltration procedure employed to fractionate blood there are several other important problems which attend the continuous plasmapheresis of blood wherein cellular components of the blood are continually returned to the patient with an amount of replacement fluid equal to the volume of plasma extracted from the blood. Thus, one of the basic problems of plasmapheresis is that some of the cellular components of the blood, such as platelets for example, are very fragile and easily destroyed and therefore must be returned to the patient undergoing plasmapheresis within a time period shorter than the useful life thereof. Blood which is stored in blood banks and the like typically does not contain sufficient amounts of viable platelets, because the blood has been outside the body longer than the useful life thereof. Another problem attending continuous plasmapheresis includes the tendency of blood which is being separated by ultrafiltration to have damage occur to the clotting factors thereof. Basically there are approximately a dozen different clotting factors which can be affected, and, of course, re-injecting the cellular components back into a patient's system where the clotting factors have been adversely effected could result in a condition similar to hemophilia. Thirdly, denaturing of proteinaceous materials contained in the blood can be a problem if the blood is subjected to varying conditions outside the body for extended periods of time.
Thus, while ultrafiltration has been employed in the past either in a plasmapheresis batch system, or in a blood fractionating process in artificial kidney devices, there is not at present a process and apparatus which provides for the continuous separation of blood into plasma fractions and cellular component fractions, wherein the cellular component fractions are continuously returned to the donor with an effective amount of replacement fluid to thereby continuously separate the donor's plasma for use in transfusions, or diagnostic, or therapeutic procedures.